Beverley Cherie Millar1,2,3, John McCaughan4, Jacqueline C Rendall5, John E Moore1,2,3. 1. Department of Bacteriology, Northern Ireland Public Health Laboratory, Belfast City Hospital, Belfast, UK. 2. School of Medicine, Dentistry and Biomedical Science, The Wellcome-Wolfson Institute for Experimental Medicine, Queen's University, Belfast, UK. 3. School of Biomedical Sciences, Ulster University, Coleraine, UK. 4. Department of Medical Microbiology, The Royal Group of Hospitals, Belfast, UK. 5. Northern Ireland Regional Adult Cystic Fibrosis Centre, Level 8, Belfast City Hospital, Belfast, UK.
Abstract
INTRODUCTION: Fluoroquinolone antibiotics, namely ciprofloxacin and levofloxacin, play an important role in treating infection in cystic fibrosis (CF) and ciprofloxacin remains the last widely used and orally available antipseudomonal agent. Recently, a new fluoroquinolone, delafloxacin, has been approved by the FDA for the indication of Acute Bacterial Skin and Skin Structure Infections (ABSSSI). This antibiotic is a novel dual-targeting anionic fluoroquinolone and differs from previous agents in its class, as it lacks a protonatable substituent. To date, there are no reports of its use or activity against Pseudomonas aeruginosa in CF. Alarmingly, fluoroquinolone resistance is increasing among CF P aeruginosa isolates. The aims of the study were to (a) examine in vitro susceptibility of delafloxacin against a population of P. aeruginosa (n = 52) isolated from adult CF patients at our CF centre, (b) to compare delafloxacin and ciprofloxacin in vitro susceptibilities against CF P. aeruginosa and (c) to evaluate where delafloxacin may add benefit in treating CF P aeruginosa. METHODS: In vitro susceptibilities were examined on 52 non-mucoid P. aeruginosa and P. aeruginosa ATCC™ 27853 reference strain, by employing Etest® gradient test strips for delafloxacin (range:0.002 - 32 mg/L) and ciprofloxacin (0.002 - 32 mg/L), as per manufacturer's instructions (Biomerieux). RESULTS: MIC range, MIC50 and MIC90 for delafloxacin were 0.064 → 32 mg/L, 0.56 mg/L and 2.19 mg/L, respectively. For ciprofloxacin, these were 0.047 → 32 mg/L, 1.69 mg/L and 8.0 mg/L, respectively. Overall, isolates were statistically more sensitive to delafloxacin (p = 0.0005) than ciprofloxacin. Of note, 4/12 (33.3%) isolates with intermediate resistance to ciprofloxacin were sensitive to delafloxacin. Similarly, 10/28 (35.7%) isolates resistant to ciprofloxacin were sensitive to delafloxacin, with only 17.9% isolates resistant to ciprofloxacin, resistant to delafloxacin. CONCLUSION: Given similar breakpoints of these fluoroquinolones, these data show that delafloxacin has greater activity than ciprofloxacin. While delafloxacin and ciprofloxacin were equally effective with sensitive isolates, the value of delafloxacin was noted with more resistant isolates to ciprofloxacin. While ciprofloxacin should remain the first line fluoroquinolone for treating CF P aeruginosa, delafloxacin shows potential in treating ciprofloxacin-resistant P aeruginosa.
INTRODUCTION:Fluoroquinolone antibiotics, namely ciprofloxacin and levofloxacin, play an important role in treating infection in cystic fibrosis (CF) and ciprofloxacin remains the last widely used and orally available antipseudomonal agent. Recently, a new fluoroquinolone, delafloxacin, has been approved by the FDA for the indication of Acute Bacterial Skin and Skin Structure Infections (ABSSSI). This antibiotic is a novel dual-targeting anionic fluoroquinolone and differs from previous agents in its class, as it lacks a protonatable substituent. To date, there are no reports of its use or activity against Pseudomonas aeruginosa in CF. Alarmingly, fluoroquinolone resistance is increasing among CF P aeruginosa isolates. The aims of the study were to (a) examine in vitro susceptibility of delafloxacin against a population of P. aeruginosa (n = 52) isolated from adult CF patients at our CF centre, (b) to compare delafloxacin and ciprofloxacin in vitro susceptibilities against CF P. aeruginosa and (c) to evaluate where delafloxacin may add benefit in treating CF P aeruginosa. METHODS: In vitro susceptibilities were examined on 52 non-mucoid P. aeruginosa and P. aeruginosa ATCC™ 27853 reference strain, by employing Etest® gradient test strips for delafloxacin (range:0.002 - 32 mg/L) and ciprofloxacin (0.002 - 32 mg/L), as per manufacturer's instructions (Biomerieux). RESULTS: MIC range, MIC50 and MIC90 for delafloxacin were 0.064 → 32 mg/L, 0.56 mg/L and 2.19 mg/L, respectively. For ciprofloxacin, these were 0.047 → 32 mg/L, 1.69 mg/L and 8.0 mg/L, respectively. Overall, isolates were statistically more sensitive to delafloxacin (p = 0.0005) than ciprofloxacin. Of note, 4/12 (33.3%) isolates with intermediate resistance to ciprofloxacin were sensitive to delafloxacin. Similarly, 10/28 (35.7%) isolates resistant to ciprofloxacin were sensitive to delafloxacin, with only 17.9% isolates resistant to ciprofloxacin, resistant to delafloxacin. CONCLUSION: Given similar breakpoints of these fluoroquinolones, these data show that delafloxacin has greater activity than ciprofloxacin. While delafloxacin and ciprofloxacin were equally effective with sensitive isolates, the value of delafloxacin was noted with more resistant isolates to ciprofloxacin. While ciprofloxacin should remain the first line fluoroquinolone for treating CF P aeruginosa, delafloxacin shows potential in treating ciprofloxacin-resistant P aeruginosa.
Authors: Jürgen Panholzer; Matthias Neuboeck; Guangyu Shao; Sven Heldt; Markus Winkler; Paul Greiner; Norbert Fritsch; Bernd Lamprecht; Helmut Salzer Journal: Case Rep Pulmonol Date: 2022-02-16